The objective of this study is to investigate the interaction of anti-tumor drugs with DNA and to investigate mechanism by which lesions created by anti-tumor drugs are repaired by cellular mechanism. 1. Neocarzinostatin. We demonstrated that neocarzinostatin cleaves DNA selectively at positions of adenosine and thymidine. 2. Bleomycin and bleomycin analogs. We have demonstrated that bleomycin cleaves DNA preferentially at pyrimidines that are located 3' to guanosine. 3. Adriamycin. Generation of adriamycin free radicals in reactions that contain NADPH and NADPH cytochrome c reductase results in cleavage of DNA. These studies are relevant to an understanding of the mechanism of action of anti-tumor drugs. Such knowledge is required to improve the use of these drugs for chemotherapy and to permit the development of new drugs.